Purpose. The safety, feasibility, and early efficacy of subfascial endoscopic perforator surgery (SEPS) for the treatment of chronic venous insufficiency were established in a preliminary report. The long-term clinical outcome and the late complications after SEPS are as yet undetermined. Methods: The North American Subfascial Endoscopic Perforator Surgery registry collected informarion on 148 SEPS procedures that were performed in 17 centers in the United States and Canada between August 1, 1993, and February 15, 1996. The data analysis in this study focused on mid- term outcome in 146 patients. Results: One hundred forty-six patients (79 men and 67 women; mean age, 56 years; range, 27 to 87 years) underwent SEPS. One hundred and one patients (69%) had active ulcers (class 6), and 21 (14%) had healed ulcers (class 5). One hundred and three patients (71%) underwent concomitant venous procedures (stripping, 70; high ligation, 17; varicosity avulsion alone, 16). There were no deaths or pulmonary embolisms. One deep venous thrombosis occurred at 2 months. The follow-up periods averaged 24 months (range, 1 to 53 months). Cumulative ulcer healing at 1 year was 88% (median time to healing, 54 days). Concomitant ablation of superficial reflux and lack of deep venous obstruction predicted ulcer healing (P < .05). Clinical score improved from 8.93 to 3.98 at the last follow-up (P < .0001). Cumulative ulcer recurrence at 1 year was 16% and at 2 years was 28% (standard error, < 10%). Post-thrombotic limbs had a higher 2-year cumulative recurrence rate (46%) than did those limbs with primary valvular incompetence (20%; P < .05). Twenty-eight of the 122 patients (23%) who had class 5 or class 6 ulcers before surgery had an active ulcer at the last follow-up examination. Conclusions: The interruption of perforators with ablation of superficial reflux is effective in decreasing the symptoms of chronic venous insufficiency and rapidly healing ulcers. Recurrence or new ulcer development, however, is still significant, particularly in post-thrombotic limbs. The reevaluation of the indications for SEPS is warranted because operations in patients without previous deep vein thrombosis are successful but operations in those patients with deep vein thrombosis are less successful. Operations on patients with deep vein occlusion have poor outcomes.